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Objective The COVID-19 pandemic has brought about a major upheaval in the lives of older adults and their family/friend caregivers, including those utilizing home care services. In this article, we focus on results from a qualitative component added to a pragmatic randomized controlled trial that focuses on the experiences of our study participants during COVID-19. A total of 29 participants responded to the COVID-19 related questions focused on their health services experiences and preferences from March-June 2020 including 10 home care clients and 19 family/friend caregivers in the provinces of Ontario and Nova Scotia, Canada. Results Many participants were affected drastically by the elimination or reduction of access to services, highlighting the vulnerability of home care clients and their caregivers during COVID-19. This took an emotional toll on home care clients and increased the need for family/friend caregiver support. While many participants expressed reduced desire to utilize residential long-term care homes, some caregivers found that passive remote monitoring technology was particularly useful within the COVID-19 context. Our results provide important insights into the ways the older adults and their caregivers have been affected during the COVID-19 context and how to better support them in the future.

Mycoprotein is a fungal-based meat alternative sold in food retail in various countries around the world. The present study builds on a multi-national sample and uses partial least square structural equation modeling. The proposed conceptual model identified key factors that are driving and inhibiting consumer willingness to try, buy, and pay a price premium for mycoprotein. The results relate to the overall sample of 4088 respondents and to two subsample comparisons based on gender and meat consumption behavior. The results show that the biggest drivers of willingness to consume mycoprotein were healthiness, followed by nutritional benefits, safe to eat, and sustainability. Affordability and taste had mixed results. Willingness to consume mycoprotein was inhibited if nutritional importance was placed on meat and, to a lesser extent, if the taste, texture, and smell of meat were deemed important. Best practice recommendations address issues facing marketing managers in the food industry.

The authors find that cell-intrinsic activation of Hedgehog signaling without genetic alterations is a contributing feature to the progression and chemotherapy resistance of small-cell lung carcinoma, and that Hedgehog inhibition can prevent lung cancer growth and recurrence. Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer for which there is no effective treatment 1 , 2 . Using a mouse model in which deletion of Rb1 and Trp53 in the lung epithelium of adult mice induces SCLC 3 , 4 , we found that the Hedgehog signaling pathway is activated in SCLC cells independently of the lung microenvironment. Constitutive activation of the Hedgehog signaling molecule Smoothened (Smo) promoted the clonogenicity of human SCLC in vitro and the initiation and progression of mouse SCLC in vivo . Reciprocally, deletion of Smo in Rb1 and Trp53 -mutant lung epithelial cells strongly suppressed SCLC initiation and progression in mice. Furthermore, pharmacological blockade of Hedgehog signaling inhibited the growth of mouse and human SCLC, most notably following chemotherapy. These findings show a crucial cell-intrinsic role for Hedgehog signaling in the development and maintenance of SCLC and identify Hedgehog pathway inhibition as a therapeutic strategy to slow the progression of disease and delay cancer recurrence in individuals with SCLC.

Previous cholecystectomy is common in patients with short bowel syndrome (SBS). An intact gallbladder is beneficial in preventing cirrhosis in SBS patients, but the nutritional consequences of cholecystectomy are largely unknown. Our aim was to evaluate the effect of pre-SBS cholecystectomy on need for chronic parenteral nutrition (PN). We reviewed 485 adults with SBS: 267 underwent cholecystectomy prior to SBS and 218 patients had an intact gallbladder. Demographic data, intestinal anatomy, and nutritional outcome were compared. Pre-SBS cholecystectomy patients were more likely to have had postoperative SBS and BMI >35. Intestinal remnant length and anatomy type and performance of surgical rehabilitation procedures within the first year were similar. Overall, there was no significant difference in the need for PN > 1year between the two groups. There was also no significant difference in the need for PN > 1year in any specific subgroup of intestinal remnant length or intestinal anatomy. Cholecystectomy performed prior to the development of SBS does not influence the nutritional prognosis of SBS, regardless of the intestinal remnant length and anatomy type. •Cholecystectomy is common in short bowel syndrome (SBS) patients.•Cholecystectomy in SBS patients increases the risk of liver fibrosis/cirrhosis.•Cholecystectomy prior to development of SBS does not alter need for chronic parenteral nutrition.•This effect is not influenced by intestinal length or anatomy.

Single-cell assay for transposase-accessible chromatin by sequencing (scATAC-seq) has emerged as a powerful tool for dissecting regulatory landscapes and cellular heterogeneity. However, an exploration of systemic biases among scATAC-seq technologies has remained absent. In this study, we benchmark the performance of eight scATAC-seq methods across 47 experiments using human peripheral blood mononuclear cells (PBMCs) as a reference sample and develop PUMATAC, a universal preprocessing pipeline, to handle the various sequencing data formats. Our analyses reveal significant differences in sequencing library complexity and tagmentation specificity, which impact cell-type annotation, genotype demultiplexing, peak calling, differential region accessibility and transcription factor motif enrichment. Our findings underscore the importance of sample extraction, method selection, data processing and total cost of experiments, offering valuable guidance for future research. Finally, our data and analysis pipeline encompasses 169,000 PBMC scATAC-seq profiles and a best practices code repository for scATAC-seq data analysis, which are freely available to extend this benchmarking effort to future protocols. Benchmarking of scATAC-seq protocols demonstrates the effects of data quality on downstream analyses.

Textbook outcome (TO) is a single composite score representing ideal care for a procedure or medical condition. Short bowel syndrome (SBS) patients are at high risk for complications and death. Our aim was to determine the incidence of and predictive factors for a TO in SBS patients. 515 adults with SBS were followed for 12 months after initial hospital discharge for SBS. TO was defined based on eight outcome parameters. Demographic data, intestinal anatomy, and nutritional outcome were compared in patients with and without TO. 78 (15 ​%) patients had a TO. The frequency of the different components of TO were: PN ​< ​1 year (39 ​%), BMI >18.5 ​kg/m2 (89 ​%), no stoma (59 ​%), no surgical intervention (71 ​%), no hospital readmission (56 ​%), no vascular access infection (62 ​%), absence of end stage liver disease (96 ​%), and survival (97 ​%). Intestinal remnant length and anatomy type were predictive of a TO. A TO is achieved in 15 ​% SBS patients using the selected criteria. This is largely attributable to continued need for PN. Intestinal length and anatomy were independent predictors of TO. •Textbook outcome as defined was achieved in 15 ​% of patients.•Continued PN dependence greater than 1 year was the most frequent reason for not achieving a textbook outcome.•Intestinal remnant length and anatomy were predictive of a textbook outcome.

Insects as an alternative protein source has gained traction for its advantageous environmental impact. Despite being part of many traditional food cultures, insects remain a novelty in Western cultures and a challenging concept for many. Even though plant-based protein alternatives are not facing the same barriers, product unfamiliarity and limited exposure hinder adoption, which could be detrimental to growth within the food sector. This study is aimed at evaluating plant- and insect-based proteins as alternative dietary proteins. A model indicating the drivers of consumer attitudes towards meat-alternative proteins and consumer willingness to try, buy, and pay a premium was tested. Further, 3091 responses were collected using surveys in nine countries: China, USA, France, UK, New Zealand, Netherlands, Brazil, Spain, and the Dominican Republic. Structural Equation Modelling was used to analyze the data. We found that consumer’s behavioral intentions towards both plant-based and insect-based alternatives are inhibited by food neophobia but to an extent, are amplified by the perceived suitability and benefits of the protein, which in turn are driven by nutritional importance, environmental impact, healthiness, and sensory attributes for both alternatives. The expectation of the nutritional value of meat is the strongest (negative) influence on perceived suitability/benefits of plant-based protein and willingness to try, buy, and pay more for plant-based proteins, but it only has a relatively small impact on the suitability/benefits of insect-based protein and no impact on willingness to try, buy, and pay more for insect-based proteins. Overall, we conclude that consumer adoption towards meat alternatives is complex and is strengthened by the perceived suitability/benefits of the protein and general importance of perceived food healthiness and sustainability. Conversely, adoption is hindered by dietary factors and the experiential importance of meat and food neophobia.

Background Obesity is an established modifiable risk factor for multiple myeloma (MM). However, associations of obesity and MM risk in Black populations, for whom obesity and MM are more common, is less clear. Methods Using participants enrolled in the Integrative Molecular And Genetic Epidemiology study, we evaluated the association of anthropometric traits with MM risk overall, stratified by race and sex. Among cases, we assessed the association of BMI with the presence of myeloma-defining events. Results We observed an 18% increase in MM risk for every 5 kg/m 2 increase in usual adult BMI. Participants with severe obesity (BMI ≥ 40 kg/m 2 ) had the highest risk compared to those with a normal usual adult BMI (18.5–24.9 kg/m 2 ; OR = 1.87, 95% CI 1.25–2.80), particularly among Black men (OR = 3.94, 95% CI 0.90–17.36). Furthermore, MM cases with overweight/obesity (BMI ≥ 25 kg/m 2 ) were more likely to present at diagnosis with low renal function (OR = 1.62, 95% CI 1.09–2.40), deletion 13q (OR = 1.73, 95% CI 1.08–2.76) and lytic lesions or compression fractures (OR = 2.39, 95% CI 0.82–7.01) and less likely to present with severe diffuse osteopenia (OR = 0.51, 95% CI 0.31–0.81). Conclusions Findings underscore the importance of obesity as a modifiable risk factor for MM, particularly in high-risk populations, and for the clinical presentation of disease.

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive, metabolic disorder caused by mutations of alanine-glyoxylate aminotransferase (AGT), a key hepatic enzyme in the detoxification of glyoxylate arising from multiple normal metabolic pathways to glycine. Accumulation of glyoxylate, a precursor of oxalate, leads to the overproduction of oxalate in the liver, which accumulates to high levels in kidneys and urine. Crystalization of calcium oxalate (CaOx) in the kidney ultimately results in renal failure. Currently, the only treatment effective in reduction of oxalate production in patients who do not respond to high-dose vitamin B6 therapy is a combined liver/kidney transplant. We explored an alternative approach to prevent glyoxylate production using Dicer-substrate small interfering RNAs (DsiRNAs) targeting hydroxyacid oxidase 1 (HAO1) mRNA which encodes glycolate oxidase (GO), to reduce the hepatic conversion of glycolate to glyoxylate. This approach efficiently reduces GO mRNA and protein in the livers of mice and nonhuman primates. Reduction of hepatic GO leads to normalization of urine oxalate levels and reduces CaOx deposition in a preclinical mouse model of PH1. Our results support the use of DsiRNA to reduce liver GO levels as a potential therapeutic approach to treat PH1.

Cholelithiasis is common in patients with short bowel syndrome (SBS). Prophylactic cholecystectomy (PC) of the non-diseased gallbladder has been recommended in SBS patients when laparotomy is being undertaken for other reasons. Our aim was to determine if PC is being utilized. 500 adults with SBS were seen over a 25 year period. 215 undergoing cholecystectomy prior to SBS were excluded, leaving 285 patients for evaluation. 151 (53%) SBS patients underwent a subsequent laparotomy. 77 underwent cholecystectomy for cholelithiasis at the 1st opportunity. 27 patients underwent a PC at the 1st opportunity. 47 patients did not undergo PC at the 1st opportunity. 17 (36%) of these 47 patients subsequently developed cholelithiasis with 7 undergoing cholecystectomy. Age, gender, diagnosis and initial BMI and need for longterm parenteral nutrition were similar in patients who had PC or did not. PC patients were more likely to have intestinal remnant length <60 cm (59% vs 21%, p < .05). Overall 10% of SBS patients underwent PC. However, only 36% of eligible patients undergoing laparotomy had a PC. •Short Bowel Syndrome is associated with the development of cholelithiasis.•Prophylactic Cholecystectomy has been recommended when short bowel patients undergo laparotomy for other reasons.•In a tertiary center, only one-third of eligible patients underwent prophylactic cholecystectomy.